Anti-prothrombin autoantibodies enriched after infection with SARS-CoV-2 and influenced by strength of antibody response against SARS-CoV-2 proteins

PLoS Pathog. 2021 Dec 3;17(12):e1010118. doi: 10.1371/journal.ppat.1010118. eCollection 2021 Dec.

Abstract

Antiphospholipid antibodies (aPL), assumed to cause antiphospholipid syndrome (APS), are notorious for their heterogeneity in targeting phospholipids and phospholipid-binding proteins. The persistent presence of Lupus anticoagulant and/or aPL against cardiolipin and/or β2-glycoprotein I have been shown to be independent risk factors for vascular thrombosis and pregnancy morbidity in APS. aPL production is thought to be triggered by-among other factors-viral infections, though infection-associated aPL have mostly been considered non-pathogenic. Recently, the potential pathogenicity of infection-associated aPL has gained momentum since an increasing number of patients infected with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has been described with coagulation abnormalities and hyperinflammation, together with the presence of aPL. Here, we present data from a multicentric, mixed-severity study including three cohorts of individuals who contracted SARS-CoV-2 as well as non-infected blood donors. We simultaneously measured 10 different criteria and non-criteria aPL (IgM and IgG) by using a line immunoassay. Further, IgG antibody response against three SARS-CoV-2 proteins was investigated using tripartite automated blood immunoassay technology. Our analyses revealed that selected non-criteria aPL were enriched concomitant to or after an infection with SARS-CoV-2. Linear mixed-effects models suggest an association of aPL with prothrombin (PT). The strength of the antibody response against SARS-CoV-2 was further influenced by SARS-CoV-2 disease severity and sex of the individuals. In conclusion, our study is the first to report an association between disease severity, anti-SARS-CoV-2 immunoreactivity, and aPL against PT in patients with SARS-CoV-2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Autoantibodies / blood*
  • COVID-19 / complications
  • COVID-19 / immunology
  • Cell Communication / immunology
  • Humans
  • Immunoglobulin G / immunology*
  • Prothrombin / immunology*
  • Risk Factors
  • SARS-CoV-2 / immunology*
  • Severity of Illness Index

Substances

  • Autoantibodies
  • Immunoglobulin G
  • Prothrombin

Grants and funding

We acknowledge funding by a grant of the Innovation Fund (INNOV00096) of the University Hospital Zurich to AA and ME. Institutional core funding by the University of Zurich and the University Hospital of Zurich as well as Driver Grant 2017DRI17 of the Swiss Personalized Health Network and an Advanced Grant of the European Research Council (ERC Prion2020, 670958), and a Distinguished Scientist Award of the Nomis Foundation were granted to AA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.